Genomes and Genes
platelet activating factor
Summary: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
- Kasperska Zajac A, Brzoza Z, Rogala B. Platelet-activating factor (PAF): a review of its role in asthma and clinical efficacy of PAF antagonists in the disease therapy. Recent Pat Inflamm Allergy Drug Discov. 2008;2:72-6 pubmed..This review is a brief summary of relevant scientific basis as well as clinical research on the role of PAF in asthma, the significance of anti-PAF therapy in the disease, as well as US. patents (1998-2002) related to PAF antagonists. ..
- Jeong Y, Jung I, Lee C, Chang J, Chun S, Noh K, et al. The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock. PLoS ONE. 2009;4:e6503 pubmed publisher..Taken together, these results suggest that PAF may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators. ..
- Tsantila N, Tsoupras A, Fragopoulou E, Antonopoulou S, Iatrou C, Demopoulos C. In vitro and in vivo effects of statins on platelet-activating factor and its metabolism. Angiology. 2011;62:209-18 pubmed publisherb>Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD). Statins are widely used in these situations. Therefore, we assessed their effect on the biological activities and metabolism of PAF...
- Welch E, Naikawadi R, Li Z, Lin P, Ishii S, Shimizu T, et al. Opposing effects of platelet-activating factor and lyso-platelet-activating factor on neutrophil and platelet activation. Mol Pharmacol. 2009;75:227-34 pubmed publisher..These findings identify lysoPAF as a bioactive lipid with opposing functions of PAF and suggest a novel and intrinsic regulatory mechanism for balance of the potent activity of PAF. ..
- Sánchez F, Rana R, González F, Iwahashi T, Duran R, Fulton D, et al. Functional significance of cytosolic endothelial nitric-oxide synthase (eNOS): regulation of hyperpermeability. J Biol Chem. 2011;286:30409-14 pubmed publisher..Our results demonstrate that the presence of eNOS in the cytosol is necessary for PAF-induced hyperpermeability. Our data provide new insights into the dynamics of eNOS and eNOS-derived NO in the process of inflammation. ..
- Liu W, Ding W, Gu H, Chen M, Hu J. Lipopolysaccharide-induced cerebral inflammatory damage and the therapeutic effect of platelet activating factor receptor antagonist. Neurosci Bull. 2007;23:271-6 pubmed..LPS can induce inflammatory damages to the brain, but the damage could be antagonized by BN52021. Platelet activating factor receptor antagonist may offer an effective therapy for neurodegeneration diseases.
- ..This Seminar looks at the changing epidemiology of this allergy--and theories as to the rise in prevalence, diagnosis, and management of the allergy, and potential new treatments and prevention strategies under development. ..
- Patel M, Kurek C, Dong Q. The arachidonic acid pathway and its role in prostate cancer development and progression. J Urol. 2008;179:1668-75 pubmed publisher..on prostate cancer and arachidonic acid, phospholipase, cyclooxygenase, lipoxygenase, epoxygenase, platelet activating factor, prostaglandin and eicosanoid...
- Egea L, Gimenez R, Lúcia D, Modolell I, Badia J, Baldoma L, et al. Increased production of the ether-lipid platelet-activating factor in intestinal epithelial cells infected by Salmonella enteritidis. Biochim Biophys Acta. 2008;1781:270-6 pubmed publisher..This response is Ca(2+)-dependent. ..
- Chini M, Tsoupras A, Mangafas N, Tsogas N, Papakonstantinou V, Fragopoulou E, et al. Effects of highly active antiretroviral therapy on platelet activating factor metabolism in naive HIV-infected patients: ii) study of the abacavir/lamivudine/efavirenz HAART regimen. Int J Immunopathol Pharmacol. 2012;25:247-58 pubmed..This finding supports the hypothesis of inflammation-mediated increased cardiovascular risk in HIV-infected patients during the first months of abacavir-containing HAART. ..
- Borthakur A, Bhattacharyya S, Alrefai W, Tobacman J, Ramaswamy K, Dudeja P. Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent. Inflamm Bowel Dis. 2010;16:593-603 pubmed publisher..The proinflammatory effects of PAF play prominent roles in the pathogenesis of IBD and this pathway may present important targets for intervention in chronic inflammatory diseases of the intestine. ..
- Singh T, Huettner B, Koefeler H, Mayer G, Bambach I, Wallbrecht K, et al. Platelet-activating factor blockade inhibits the T-helper type 17 cell pathway and suppresses psoriasis-like skin disease in K5.hTGF-?1 transgenic mice. Am J Pathol. 2011;178:699-708 pubmed publisher..Interfering with PAF may offer the opportunity to develop novel therapeutic strategies for inflammatory psoriasis and associated comorbidities, including metabolic syndrome and atherosclerosis, in which the IL-17 axis may be involved. ..
- Kasperska Zajac A, Brzoza Z, Rogala B. Platelet activating factor as a mediator and therapeutic approach in bronchial asthma. Inflammation. 2008;31:112-20 pubmed publisherb>Platelet activating factor (PAF) is a potent phospholipid mediator involved in anaphylaxis and chronic inflammatory disorders, including bronchial asthma...
- Chen J, Yang L, Foulks J, Weyrich A, Marathe G, McIntyre T. Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesis. J Lipid Res. 2007;48:2365-76 pubmed
- Claud E, Lu J, Wang X, Abe M, Petrof E, Sun J, et al. Platelet-activating factor-induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1191-200 pubmed publisher..Our data suggest a novel mechanism of PAF-induced injury by which PAF induces intracellular acidosis via activation of the Ca(2+)-dependent Cl(-) channel ClC-3, resulting in apoptosis of IEC. ..
- van Zoelen M, Florquin S, Meijers J, de Beer R, de Vos A, de Boer O, et al. Platelet-activating factor receptor contributes to host defense against Pseudomonas aeruginosa pneumonia but is not essential for the accompanying inflammatory and procoagulant response. J Immunol. 2008;180:3357-65 pubmed..Additionally, our results indicate that PAFR signaling is not essential for the induction of a local and systemic inflammatory and procoagulant response to Pseudomonas pneumonia. ..
- Vadas P, Gold M, Perelman B, Liss G, Lack G, Blyth T, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358:28-35 pubmed publisher..The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported...
- Detopoulou P, Nomikos T, Fragopoulou E, Antonopoulou S, Kotroyiannis I, Vassiliadou C, et al. Platelet activating factor (PAF) and activity of its biosynthetic and catabolic enzymes in blood and leukocytes of male patients with newly diagnosed heart failure. Clin Biochem. 2009;42:44-9 pubmed publisherTo evaluate platelet activating factor (PAF) levels, its metabolic enzymes activity and its associations with other inflammatory markers in heart failure (HF) patients...
- Giannattasio G, Lai Y, Granata F, Mounier C, Nallan L, Oslund R, et al. Expression of phospholipases A2 in primary human lung macrophages: role of cytosolic phospholipase A2-alpha in arachidonic acid release and platelet activating factor synthesis. Biochim Biophys Acta. 2009;1791:92-102 pubmed publisher..Our results indicate that human macrophages express cPLA(2)-alpha, iPLA(2) and several sPLA(2)s. Cytosolic PLA(2)-alpha is the major enzyme responsible for lipid mediator production in human macrophages. ..
- McIntyre T, Prescott S, Stafforini D. The emerging roles of PAF acetylhydrolase. J Lipid Res. 2009;50 Suppl:S255-9 pubmed publisher..The roles of these enzymes are manifold, and their separate and combined functions are now being addressed in model systems and clinical studies. ..
- Lu J, Pierce M, Franklin A, Jilling T, Stafforini D, Caplan M. Dual roles of endogenous platelet-activating factor acetylhydrolase in a murine model of necrotizing enterocolitis. Pediatr Res. 2010;68:225-30 pubmed publisher..In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and because preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. ..
- Marotta D, Costa R, Motta E, Fernandes E, Medeiros R, Quintão N, et al. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw. Biochem Pharmacol. 2009;77:1223-35 pubmed..They also support the concept that selective PAF receptor antagonists might constitute interesting targets for the development of new analgesic drugs. ..
- Xu L, Teng X, Guo J, Sun M. Protective effect of intestinal trefoil factor on injury of intestinal epithelial tight junction induced by platelet activating factor. Inflammation. 2012;35:308-15 pubmed publisher..These results suggest that ITF decreases mucosal permeability and shows potential as a therapy for treating IBD. ..
- Liu J, Chen R, Marathe G, Febbraio M, Zou W, McIntyre T. Circulating platelet-activating factor is primarily cleared by transport, not intravascular hydrolysis by lipoprotein-associated phospholipase A2/ PAF acetylhydrolase. Circ Res. 2011;108:469-77 pubmed publisher..Intravascular PAF has access to intracellular compartments. Inflammatory and proapoptotic phospholipids may accumulate in the circulation as transport is overwhelmed by substrates in hyperlipidemia. ..
- Howard K, Abdel Al M, Ditmyer M, Patel N. Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways. Inflamm Res. 2011;60:735-44 pubmed publisher..PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent. The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways. ..
- Sahu R, Kozman A, Yao Y, Dasilva S, Rezania S, Martel K, et al. Loss of the platelet activating factor receptor in mice augments PMA-induced inflammation and cutaneous chemical carcinogenesis. Carcinogenesis. 2012;33:694-701 pubmed publisher..This suggests that the platelet activating factor receptor (PAFR) acts to suppress chronic inflammation in response to other stimuli, such as barrier ..
- Seki M, Kosai K, Hara A, Imamura Y, Nakamura S, Kurihara S, et al. Expression and DNA microarray analysis of a platelet activating factor-related molecule in severe pneumonia in mice due to influenza virus and bacterial co-infection. Jpn J Infect Dis. 2009;62:6-10 pubmed..These findings suggest that PAF and related molecules play important roles in fulminant pneumonia due to influenza virus infection, especially when severe bacterial pneumonia is complicated by co-infection with influenza virus. ..
- Tsoupras A, Chini M, Tsogas N, Fragopoulou E, Nomikos T, Lioni A, et al. Anti-platelet-activating factor effects of highly active antiretroviral therapy (HAART): a new insight in the drug therapy of HIV infection?. AIDS Res Hum Retroviruses. 2008;24:1079-86 pubmed publisher..These promising results need to be further studied and confirmed by additional in vivo tests in order to optimize HAART efficacy. ..
- Tsoupras A, Papakyriakou A, Demopoulos C, Philippopoulos A. Synthesis, biochemical evaluation and molecular modeling studies of novel rhodium complexes with nanomolar activity against Platelet Activating Factor. J Inorg Biochem. 2013;120:63-73 pubmed publisher..On the other hand, the octahedral rhodium(III) complexes 3-5 that cannot fit the ligand-binding domain, could potentially exhibit their activity at the extracellular domain of the receptor...
- Nasopoulou C, Tsoupras A, Karantonis H, Demopoulos C, Zabetakis I. Fish polar lipids retard atherosclerosis in rabbits by down-regulating PAF biosynthesis and up-regulating PAF catabolism. Lipids Health Dis. 2011;10:213 pubmed publisherb>Platelet activating factor (PAF) has been proposed as a key factor and initial trigger in atherosclerosis. Recently, a modulation of PAF metabolism by bioactive food constituents has been suggested...
- Jönsson F, Mancardi D, Kita Y, Karasuyama H, Iannascoli B, Van Rooijen N, et al. Mouse and human neutrophils induce anaphylaxis. J Clin Invest. 2011;121:1484-96 pubmed publisher..These molecules and cells could be potential new targets for the development of anaphylaxis therapeutics if the same mechanism is responsible for anaphylaxis in humans...
- Belanger C, Elimam H, Lefebvre J, Borgeat P, Marleau S. Involvement of endogenous leukotriene B4 and platelet-activating factor in polymorphonuclear leucocyte recruitment to dermal inflammatory sites in rats. Immunology. 2008;124:295-303 pubmed publisher..Our results strongly support a role of both endogenous LTB(4) and PAF in regulating PMN trafficking to inflammatory sites in various experimental conditions. ..
- Morita K, Kitayama T, Morioka N, Dohi T. Glycinergic mediation of tactile allodynia induced by platelet-activating factor (PAF) through glutamate-NO-cyclic GMP signalling in spinal cord in mice. Pain. 2008;138:525-36 pubmed publisher..These results suggest that the glutamate-NO-cGMP-PKG pathway in the spinal cord may be involved in the mechanism of PAF-induced tactile allodynia, and GlyR alpha3 could be a target molecule through which PKG induces allodynia. ..
- Corl C, Gandy J, Sordillo L. Platelet activating factor production and proinflammatory gene expression in endotoxin-challenged bovine mammary endothelial cells. J Dairy Sci. 2008;91:3067-78 pubmed publisher..b>Platelet activating factor (PAF), interleukin 1 beta (IL-1 beta), IL-8, and intercellular adhesion molecule 1 (ICAM1) are among the ..
- Li J, Hu J, Shao B, Zhou W, Cui Y, Dong C, et al. Protection of PMS777, a new AChE inhibitor with PAF antagonism, against amyloid-beta-induced neuronal apoptosis and neuroinflammation. Cell Mol Neurobiol. 2009;29:589-95 pubmed publisher..These results suggest that PMS777 potently protects against Abeta-induced neuronal apoptosis and neuroinflammation, and warrants further investigations in connection with its potential value in the treatment of Alzheimer's disease. ..
- Kordan W, Lecewicz M, Strzezek R, Dziekońska A, Fraser L. Effect of platelet activating factor (PAF) supplementation in semen extender on viability and ATP content of cryopreserved canine spermatozoa. Pol J Vet Sci. 2010;13:571-9 pubmedThe aim of this study was to investigate the effect of platelet activating factor (PAF) on the quality characteristics of cryopreserved canine spermatozoa...
- Fragel Madeira L, Meletti T, Mariante R, Monteiro R, Einicker Lamas M, Bernardo R, et al. Platelet activating factor blocks interkinetic nuclear migration in retinal progenitors through an arrest of the cell cycle at the S/G2 transition. PLoS ONE. 2011;6:e16058 pubmed publisherNuclear migration is regulated by the LIS1 protein, which is the regulatory subunit of platelet activating factor (PAF) acetyl-hydrolase, an enzyme complex that inactivates the lipid mediator PAF...
- Edwards L, Constantinescu C. Platelet activating factor/platelet activating factor receptor pathway as a potential therapeutic target in autoimmune diseases. Inflamm Allergy Drug Targets. 2009;8:182-90 pubmedb>Platelet activating factor (PAF) is a phospholipid mediator of inflammation that is released early in inflammation by a variety of cell types...
- Donado E, Izquierdo I, Pérez I, García O, Antonijoan R, Gich I, et al. No cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a 'thorough QT/QTc study' performed according to ICH guidelines. Br J Clin Pharmacol. 2010;69:401-10 pubmed publisher..This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety. ..
- Kennedy M, Kabbani N, Lambert J, Swayne L, Ahmed F, Figeys D, et al. Srf1 is a novel regulator of phospholipase D activity and is essential to buffer the toxic effects of C16:0 platelet activating factor. PLoS Genet. 2011;7:e1001299 pubmed publisher..Together, these findings implicate PLD as a potential neuroprotective target capable of ameliorating disruptions in lipid metabolism in response to accumulating oligomeric amyloid-???. ..
- Kihara Y, Yanagida K, Masago K, Kita Y, Hishikawa D, Shindou H, et al. Platelet-activating factor production in the spinal cord of experimental allergic encephalomyelitis mice via the group IVA cytosolic phospholipase A2-lyso-PAFAT axis. J Immunol. 2008;181:5008-14 pubmed..These data suggest that PAF accumulation in the SC of EAE mice is profoundly dependent on the group IVA cytosolic PLA(2)/LysoPAFAT axis present in the infiltrating macrophages and activated microglia. ..
- Frost B, Jilling T, Caplan M. The importance of pro-inflammatory signaling in neonatal necrotizing enterocolitis. Semin Perinatol. 2008;32:100-6 pubmed publisher..In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. ..
- Whitehead S, Hou W, Ethier M, Smith J, Bourgeois A, Denis R, et al. Identification and quantitation of changes in the platelet activating factor family of glycerophospholipids over the course of neuronal differentiation by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. Anal Chem. 2007;79:8539-48 pubmed..Synthesis of the platelet activating factor (PAF) glycerophospholipid subclass is implicated in the control of neuronal differentiation and death...
- Kolovou V, Papakonstantinou V, Stamatakis G, Verouti S, Xanthopoulou M, Kolovou G, et al. Platelet activating factor levels and metabolism in Tangier disease: a case study. Lipids Health Dis. 2012;11:89 pubmed publisher..In addition, PAF can be biosynthesized from the remodeling and the de novo pathways in which Lyso-platelet activating factor-acetyltransferase (Lyso-PAF-AT) and platelet activating factor-cholinephosphotransferase (PAF-CPT) are ..
- Tsoupras A, Fragopoulou E, Nomikos T, Iatrou C, Antonopoulou S, Demopoulos C. Characterization of the de novo biosynthetic enzyme of platelet activating factor, DDT-insensitive cholinephosphotransferase, of human mesangial cells. Mediators Inflamm. 2007;2007:27683 pubmedb>Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes...
- Khodoun M, Strait R, Orekov T, Hogan S, Karasuyama H, Herbert D, et al. Peanuts can contribute to anaphylactic shock by activating complement. J Allergy Clin Immunol. 2009;123:342-51 pubmed publisher..Resistance to digestion and dendritic cell activation by the major peanut allergen Ara h 1 are reported to contribute to its allergenicity...
- Frost B, Caplan M. Necrotizing enterocolitis: pathophysiology, platelet-activating factor, and probiotics. Semin Pediatr Surg. 2013;22:88-93 pubmed publisher..This chapter reviews NEC pathophysiology, including the role of PAF, as well as literature on the use of probiotics in the preterm infant. ..